二甲双胍联合γδT细胞对喉癌治疗的效果和机制研究  

Study on the efficacy and mechanism of metformin combined with gamma delta T cells in the treatment of laryngeal cancer

作　　者：梁振源[1] 陈晓芳[1] 邱恩惠[1] 石小伟[1] Liang Zhen-yuan;Chen Xiao-fang;Qiu En-hui;Shi Xiao-wei(Fujian Medical University Affiliated Second Hospital,Quanzhou 362000,China)

机构地区：[1]福建医科大学附属第二医院,福建泉州362000

出　　处：《北方药学》2025年第1期5-9,24,共6页Journal of North Pharmacy

基　　金：福建省泉州市科技局项目(编号:2021N039S)。

摘　　要：目的:探究二甲双胍(Metformin)联合γδT细胞对喉癌治疗的效果和机制。方法:细胞实验:体外分离扩增人外周血γδT细胞,将其分为对照组(无Metformin)、低剂量组(3mmol/L的Metformin)、中剂量组(15mmol/L的Metformin)和高剂量组(75mmol/L的Metformin),检测γδT细胞增殖能力、细胞周期、细胞凋亡情况。取喉癌细胞TU212、喉癌细胞TU686作为靶细胞,收集经Metformin(浓度为75 mmol/L)作用的γδT细胞作为效应细胞,检测Metformin对γδT细胞的杀伤功能影响。动物实验:喉癌细胞TU212接种于24只裸鼠皮下构建喉癌模型,将其随机分为4组(各组6只),其中空白对照组注射生理盐水,Metformin组单纯使用Metformin治疗,γδT细胞组给予γδT细胞治疗,Metformin+γδT细胞组给予Metformin联合γδT细胞治疗,检测各组裸鼠的肿瘤体积变化情况和PD-L1蛋白表达情况。结果:(1)不同浓度Metformin处理γδT细胞下的细胞增殖率、细胞周期及细胞凋亡情况差异显示出统计学意义(P<0.05)。(2)经过Metformin作用后,γδT细胞对喉癌细胞TU212和喉癌细胞TU686的杀伤能力明显增强,其中γδT细胞:喉癌细胞比为10:1与20:1时杀伤能力差异有统计学意义(P<0.05)。(3)在裸鼠荷瘤实验模型上,单独注射Metformin对喉癌肿瘤组织生长、PD-L1蛋白表达的抑制程度最小,其次为γδT细胞治疗,Metformin联合γδT细胞治疗时对喉癌肿瘤组织的生长、PD-L1蛋白表达抑制程度最大。结论:Metformin联合γδT细胞治疗能够通过抑制PD-L1的表达来调控免疫微环境,促进γδT细胞的增殖和细胞周期,增强γδT细胞对喉癌细胞的杀伤能力,对喉癌治疗具有潜在价值。Objective:To investigate the efficacy and mechanism of metformin combined with gamma delta T cells in the treatment of laryngeal cancer.Method:Cell experiment:Human peripheral blood gamma delta T cells were isolated and expanded in vitro,and divided into control group,low-dose group,medium dose group,and high-dose group.Metformin at concentrations of 0、3、15 and 75 mmol/L was added to detect the proliferation ability,cell cycle,and apoptosis of gamma delta T cells.Take laryngeal cancer cells TU212 and TU686 as target cells,collect gamma delta T cells treated with Metformin(concentration of 75 mmol/L)as effector cells,and detect the effect of Metformin on the killing function of gamma delta T cells.Animal experiment:24 nude mice were subcutaneously inoculated with laryngeal cancer cells TU212 to construct a laryngeal cancer model.They were randomly divided into 4 groups(6 mice in each group).The blank control group was injected with physiological saline,the Metformin group was treated with Metformin alone,the gamma delta T cell group was treated with gamma delta T cells,and the Metformin+gamma delta T cell group was treated with Metformin combined with gamma delta T cells.The tumor volume changes and PD-L1 protein expression of each group of nude mice were detected.Results:(1)There were statistically significant differences(P<0.05)in the cell proliferation rate,cell cycle,and apoptosis of gamma delta T cells treated with different concentrations of Metformin.With the increase of Metformin concentration,the proliferation rate of gamma delta T cells showed an upward trend,while the G 0/G 1 phase ratio of gamma delta T cells showed a downward trend,and the S phase and G2/M phase ratios showed an upward trend.Among them,there was no statistically significant difference(P>0.05)in the cell proliferation rate,cell cycle,and apoptosis between the control group and the low-dose group,as well as the medium dose group.However,there was a statistically significant difference(P<0.05)in the cell proliferation rate,cell cycle

关 键 词：二甲双胍 ΓΔT细胞 喉癌 机制 

分 类 号：R-332[医药卫生]